Physicochemical and microbiological evaluation of acidmodified native starch derived from Borassus aethiopum (Arecaceae) shoot

Purpose: To evaluate the physicochemical properties and microbiological quality of Borassus aethiopum shoot acid-modified starch (AMS) for potential pharmaceutical applications.Methods: Modification of Borassus aethiopum native starch (NS) was carried out using 6 % w/v HCl at 37 ± 2 oC for 192 h. The AMS was characterised for their morphological, micromeritics, rheological, thermal properties as well as their microbiological quality using standard protocols.Results: AMS demonstrated increased aqueous solubility, crystallinity and slight increase in flow properties. There was a reduction in swelling and hydration capacities, amylose content as well as viscosity of the modified starch. Scanning electron microscopy analysis showed that the integrity of the modified starch granules were maintained and there was no disruption of the granular structure. Fourier transform infrared spectrophometer data confirmed the hydrolysis of NS with the increase in the intensity of the O-H stretch. AMS met United States Pharmacopoeia requirements in terms of microbiological quality, however, there was presence of Aspergillus niger.Conclusion: Modification of Borassus aethiopum shoot starch by acid treatment led to desirable improvement in some of its physicochemical properties which could improve its functional properties in pharmaceutical industries.Keywords: Native starch, Acid-modified starch, Borassus aethiopum, Microbiological quality, Physicochemical propertie

Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.

Miltefosine is the first and only oral medication to be successfully utilized as an antileishmanial agent. However, the drug is associated with differences in exposure patterns and cure rates among different population groups e.g. ethnicity and age (i.e., children v adults) in clinical trials. In this work, mechanistic population physiologically-based pharmacokinetic (PBPK) models have been developed to study the dose-exposure-response relationship of miltefosine in in silico clinical trials and evaluate the differences in population groups, particularly children and adults. The Simcyp population pharmacokinetics platform was employed to predict miltefosine exposure in plasma and peripheral blood mononuclear cells (PBMCs) in a virtual population under different dosing regimens. The cure rate of a simulation was based on the percentage of number of the individual virtual subjects with AUC  > 535 µg⋅day/mL in the virtual population. It is shown that both adult and paediatric PBPK models of miltefosine can be developed to predict the PK data of the clinical trials accurately. There was no significant difference in the predicted dose-exposure-response of the miltefosine treatment for different simulated ethnicities under the same dose regime and the dose-selection strategies determined the clinical outcome of the miltefosine treatment. A lower cure rate of the miltefosine treatment in paediatrics was predicted because a lower exposure of miltefosine was simulated in virtual paediatric in comparison with adult virtual populations when they received the same dose of the treatment. The mechanistic PBPK model suggested that the higher fraction of unbound miltefosine in plasma was responsible for a higher probability of failure in paediatrics because of the difference in the distribution of plasma proteins between adults and paediatrics. The developed PBPK models could be used to determine an optimal miltefosine dose regime in future clinical trials. [Abstract copyright: © 2023. The Author(s).

Integral Role of Water in the Solid-State Behavior of the Antileishmanial Drug Miltefosine

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Open access articleMiltefosine is a repurposed anticancer drug and currently the only orally administered drug approved to treat the neglected tropical disease leishmaniasis. Miltefosine is hygroscopic and must be stored at sub-zero temperatures. In this work we report the X-ray structures of miltefosine monohydrate and methanol solvate, along with 12- and 14-carbon chain analogue hydrates and a solvate. The three hydrates are all isostructural and are conformational isomorphs with Z' = 2. The water bridges the gap between phosphocholine head groups caused by the interdigitated bilayer structure. The two methanol solvates are also mutually isostructural with the head groups adopting a more extended conformation. Again, the solvent bridges the gap between head groups in the bilayer. No anhydrous form of miltefosine or its analogues were isolated, with dehydration resulting in significantly reduced crystallinity. This arises as a result of the integral role that hydrogen bond donors (in the form of water or solvent molecules) play in the stability of the zwitterionic structures

Artemisinin-acetylenedicarboxylic acid cocrystal: screening, structure determination, and physicochemical property characterisation

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Artemisinin is used to treat malaria, even when caused by multi-drug resistant strains of the Plasmodium parasite; the compound also shows good promise as an anti-cancer drug. However, the usage of artemisinin is limited due to its low aqueous solubility. Herein a large scale of cocrystal screening of artemisinin was conducted using both computational and experimental approaches, resulting in a new 2:1 artemisinin and acetylenedicarboxylic acid (ART2-ACA) cocrystal. ART2-ACA crystallises in the P 212121 space group of an orthorhombic system with the cell parameters a = 10.5089 Å, b = 24.083 Å, c = 6.4952 Å. The asymmetric unit of the cocrystal contains two ART molecules and a single ACA molecule, assembled into discrete trimeric units held together by two supramolecular heterosynthons. It was shown that ART2-ACA cocrystals are of higher solubility and faster dissolution rate compared to the parent drug of artemisinin

Integral Role of Water in the Solid-State Behavior of the Antileishmanial Drug Miltefosine

Miltefosine is a repurposed anticancer drug and currently the only orally administered drug approved to treat the neglected tropical disease leishmaniasis. Miltefosine is hygroscopic and must be stored at subzero temperatures. In this work, we report the X-ray structures of miltefosine monohydrate and methanol solvate, along with 12- and 14-carbon chain analogue hydrates and a solvate. The three hydrates are all isostructural and are conformational isomorphs with Z′ = 2. Water bridges the gap between phosphocholine head groups caused by the interdigitated bilayer structure. The two methanol solvates are also mutually isostructural with the head groups adopting a more extended conformation. Again, the solvent bridges the gap between head groups in the bilayer. No anhydrous form of miltefosine or its analogues were isolated, with dehydration resulting in significantly reduced crystallinity. This arises as a result of the integral role that hydrogen-bond donors (in the form of water or solvent molecules) play in the stability of the zwitterionic structures